Molecular determinants of metastatic transformation.

Abstract

In recent years, experimental systems have developed to analyze genetic and epigenetic regulation of the metastatic phenotype. Numerous studies have uncovered a potent role for transforming oncogenes in metastatic conversion. In addition, it has been shown that oncoprotein products operate in a dose-dependent fashion. The continued expression of oncoproteins is required to induce and regulate metastatic dissemination of tumor cells and, consequently, many of the signal transduction pathways that are controlled by the oncogene products can regulate metastasis. Exogenous growth factors that act through these same pathways also alter metastatic potential. Some primary and immortalized cells can be transformed by oncogenes but remain completely benign and nonmetastatic. Malignant transformation can be achieved in these cells through the cooperative interaction of specific oncogenes or loss of active suppression regulated by recessive genetic determinants. Therefore, it is likely that tumor cells acquire the metastatic phenotype through the cooperative interaction of dominant and recessive genetic alterations. This model is consistent with the correlative data accumulating in studies of human tumor specimens where more malignant carcinomas often contain both activating mutations in oncogenes and either inactivating mutations or loss of tumor-suppressor genes.

Expression of oncoproteins in primary human non-small cell lung cancer and incidence of metastases

“…In view of these wideranging observations, more detailed investigations are required to elucidate the significance of oncogenes for the formation of metastases. It is likely that tumor cells acquire the metastatic phenotype through the co-operative interaction of different dominant and recessive genetic alterations [27].…”

Expressionsanalyse des humanen Histonsubtyps H1x

“…Tumore entstehen, wenn sich bestimmte Abschnitte der Erbsubstanz verändern und diese Veränderungen nicht mehr repariert werden können. Die Ursache für die Entstehung einer malignen Transformation sind zumeist fehlerhaft regulierte Onkogene oder Tumorsuppressorgene, die ihre Funktionalität verloren haben (Bailleul et al, 1989;Egan et al, 1991;Koeffler, 1991;Lehman et al, 1991;Hanahan & Weinberg, 2000).…”